Peripheral T-cell lymphomas correlate with TFH-like features C84.4

Inactivating mutations of the ten-eleven translocation 2 (TET2) gene were first detected in myeloid malignancies. Later, they were also indexed in PTCL-NOS, a heterogeneous group of lymphomas that probably originate from Th follicular (T(FH)) cells similar to AITL, in about 40% of cases (Lemonnier Fet al. 2012). In this T-cell variant, TET2 mutations were more frequently detectable when these lymphomas expressed T(FH) markers and/or had features reminiscent of AITL. TET2 mutations were associated with advanced disease stage, thrombocytopenia, and shorter progression-free survival.

Peripheral T-cell lymphomas with a TFH phenotype were previously included in the broad category of PTCL-NOS and now represent their own provisional subgroup in the current WHO classification. TFH cells (TFH is the acronym for "follicular B helper T-cells") form a smaller subpopulation of Th lymphocytes that express CXCR5 on their surface. These cells are found within the B-cell follicles of human tonsils and in the blood.

Immunophenotypically, the neoplastic cells express Pan-T cell antigens(CD2, CD3, and CD5) with frequent deficiency of CD7. Lymphomas of this type are by definition CD4 positive and must express at least 2 (preferably 3) of the TFH markers (PD1, CD10, BCL6, CXCL13, ICOS). Interspersed CD20-positive immunoblasts are often EBV-positive. Hodgkin/Reed-Sternberg-like cells may also have the phenotype of classical Hodgkin lymphoma (CD30+, CD15+, PAX5+, EBV+/-), making lymphocyte-rich classical Hodgkin lymphoma an important differential diagnosis here. It will be seen in the future whether this subgroup represents a separate entity.

It is widely believed that this provisional subset may represent a tumor cell-rich variant of AITL.

1. Dobay MPet al. (2017) Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin. Haematologica 102:e148-e151
2. Lemonnier Fet al. (2012) Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood 120:1466-1469
3. Lemonnier Fet al (2016) The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development. Proc Natl Acad Sci U S A 113:15084-15089
4. Moon CS et al (2021) FYN-TRAF3IP2 induces NF-κB signaling-driven peripheral T-cell lymphoma. Nature Cancer 2:98-113
5. Palomero T et al (2014) Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet 46:166-170
6. Sakata-Yanagimoto M et al (2014) Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet 46:171-175
7. Timmins MA et al (2020) The new biology of PTCL-NOS and AITL: current status and future clinical impact. Br J Haematol 189:54-66.
8. Vallois D et al (2016) Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood 128:1490-1502